title: Transgenic mosquitoes expressing a phospholipase A(2) gene have a fitness advantage when fed Plasmodium falciparum-infected blood.
abstract: BACKGROUND
  Genetically modified mosquitoes have been proposed as an alternative strategy to reduce the heavy burden of malaria. In recent years, several proof-of-principle experiments have been performed that validate the idea that mosquitoes can be genetically modified to become refractory to malaria parasite development.
  
  
  RESULTS
  We have created two transgenic lines of Anophelesstephensi, a natural vector of Plasmodium falciparum, which constitutively secrete a catalytically inactive phospholipase A2 (mPLA2) into the midgut lumen to interfere with Plasmodium ookinete invasion. Our experiments show that both transgenic lines expressing mPLA2 significantly impair the development of rodent malaria parasites, but only one line impairs the development of human malaria parasites. In addition, when fed on malaria-infected blood, mosquitoes from both transgenic lines are more fecund than non-transgenic mosquitoes. Consistent with these observations, cage experiments with mixed populations of transgenic and non-transgenic mosquitoes show that the percentage of transgenic mosquitoes increases when maintained on Plasmodium-infected blood.
  
  
  CONCLUSIONS
  Our results suggest that the expression of an anti-Plasmodium effector gene gives transgenic mosquitoes a fitness advantage when fed malaria-infected blood. These findings have important implications for future applications of transgenic mosquito technology in malaria control.
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Smith
authors.forename: Christopher
authors.initials: C
authors.lastname: Kizito
authors.forename: Jason L
authors.initials: JL
authors.lastname: Rasgon
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D009033:Culicidae / Q000235:genetics* / Q000378:metabolism; D005260:Female; D023061:Gene Order; D056084:Genetic Fitness; D059765:Homologous Recombination; D006801:Humans; D008288:Malaria / Q000469:parasitology / Q000635:transmission; D016254:Mutagenesis, Insertional; D054467:Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000254:growth & development*
chemical_list: D054467:Phospholipases A2